Gene therapy using FGFR-inhibiting vector against lung squamous cell carcinoma

• Project/Area Number: 23659666
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Thoracic surgery
• Research Institution: Kyoto University
• Principal Investigator: DATE Horoshi 京都大学, 医学(系)研究科(研究院), 教授 (60252962)
• Co-Investigator(Kenkyū-buntansha): 黄 政龍 公益財団法人田附興風会医学研究所 (10271511) ; 園部 誠 京都大学, 医学(系)研究科 (00432378) ; 毛受 暁史 京都大学, 医学(系)研究科 (30527081)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: FGFR / ｓｈRNA / アデノウィルス / ベクター / 遺伝子治療 / shRNA / ＦＧＦＲ / ｓｈＲＮＡ / sh RNA

Research Abstract

We performed an experimental study on the gene therapy using a FGFR-inhibiting vector for a new treatment against lung squamous cell carcinomas. First, we have done a clinical study on the inntratumoral expressions of FGFR family genes. Consequently, we considered that not only FGFR1 but also FGR2 could be target genes for treatments. We produced a FGFR2-inhibiting vector using an adenoviral vector (Ad-shFGFR2). in vitro experiments using the Ad-shFGFR2 were performed against a lung cancer cell line A549, which has high expression levels of FGFR2. The Ad-shFGFR2 effectively knocked down the FGFR2 expression (approximately 85%). However, MTT assays revealed that the Ad-shFRFR2 did not effectively inhibit the growth of tumor cells. Therefore, considering that FGFR2 may not be a simple driver gene, we perform an experimental study using co-transfection with other candidates of driver genes.

Research Products

• [Journal Article] Use of virtual assisted lung mapping (VAL-MAP), a bronchoscopic multispot dye-marking technique using virtual images, for precise navigation of thoracoscopic sublobar lung resection (2014)
  • Author(s): Sato M, Omasa M, Chen F, Sato T, Sonobe M, Bando T, Date H
  • Journal Title: J Thorac Cardiovasc Surg Volume: 147 Pages: 1813-1819
• [Journal Article] The Japan-Multinational Trial Organization. Prognostic factors after complete resection of pN2 non-small cell lung cancer (2013)
  • Author(s): Sonobe M, Date H, Wada H, Okubo K, Hamakawa H, Teramukai S, Matsumura A, Nakagawa T, Sumitomo S, Miyamoto Y, Okumura N, Takeo S, Kawakami K, Aoki M, Kosaka S
  • Journal Title: J Thorac Cardiovasc Surg Volume: 146 Pages: 788-795
• [Journal Article] Snail expression is associated with a poor prognosis in malignantpleural mesotheliomas (2013)
  • Author(s): Kobayashi M, Huang CL, Sonobe M, Kikuchi R, Ishikawa M, Imamura N, Kitamura J, Iwakiri S, Itoi K, Yasumizu R, Date H
  • Journal Title: Ann Thorac Surg Volume: 95 Pages: 1181-1188
• [Journal Article] Higher expression of receptor tyrosine kinase Axl, and differential expression of its ligand, Gas6, predict poor survival in lung adenocarcinoma patients (2013)
  • Author(s): Ishikawa M, Sonobe M, Nakayama E, Kobayashi M, Kikuchi R, Kitamura J, Imamura N, Date H
  • Journal Title: Ann Surg Oncol Volume: 20 Suppl 3
• [Journal Article] Snail expression is associated with a poor prognosis in malignant pleural mesotheliomas. (2013)
  • Author(s): 309. Kobayashi M, Huang CL, Sonobe M, Kikuchi R, Ishikawa M, Imamura N, Kitamura J, Iwakiri S, Itoi K, Yasumizu R, Date H.
  • Journal Title: Ann Thorac Surg Volume: 95 Pages: 1181-8
  • Peer Reviewed
• [Journal Article] The Japan-Multinational Traial Organization. Prognostic factors after complete resection of pN2 non-small cell lung cancer. (2013)
  • Author(s): 319. Sonobe M, Date H, Wada H, Okubo K, Hamakawa H, Teramukai S, Matsumura A, Nakagawa T, Sumitomo S, Miyamoto Y, Okumura N, Takeo S, Kawakami K, Aoki M, Kosaka S
  • Journal Title: J Thorac Cardiovasc Surg Volume: 146 Pages: 788-95
  • Peer Reviewed
• [Journal Article] Impact of KRAS and EGFR gene mutations on recurrence and survival in patients with surgically resected lung adenocarcinomas (2012)
  • Author(s): Sonobe M, Kobayashi M, Ishikawa M, Kikuchi R, Nakayama E, Takahashi T, Menju T, Takenaka K, Miyahara R, Huang CL, Okubo K, Bando T, Date H
  • Journal Title: Ann Surg Oncol Volume: 19 Suppl 3
• [Journal Article] Intratumoral Wnt2B expression affects tumor proliferation and survival in malignant pleural mesothelioma patients (2012)
  • Author(s): Kobayashi M, Huang CL, Sonobe M, Kikuchi R, Ishikawa M, Kitamura J, Miyahara R, Menju T, Iwakiri S, Itoi K, Yasumizu R, Date H
  • Journal Title: Experimental and Therapeutic Medicine Volume: 3 Pages: 952-958
• [Journal Article] Detection of ALK fusion in lung cancer using fluorescence in situ hybridization (2012)
  • Author(s): Kobayashi M, Sonobe M, Takahashi T, Yoshizawa A, Kikuchi R, Date H
  • Journal Title: Asian Cardiovasc Thorac Ann Volume: 20 Pages: 426-431
• [Journal Article] Pharmacokinetic study of weekly (days 1-5) low-dose S-1 in patients with non-small-cell lung cancer (2012)
  • Author(s): Shoji T, Sonobe M, Sakai H, Fujinaga T, Sato T, Chen F, Miyahara R, Bando T, Wada H, Date H
  • Journal Title: Rev Recent Clin Trials Volume: 7 Pages: 167-172
  • NAID: 120005285491
• [Journal Article] Higher expression of EphA2 and ephrin-A1 is related to favorable clinicopathological features in pathological stage I non-small cell lung carcinoma (2012)
  • Author(s): Ishikawa M, Miyahara R, Sonobe M, Horiuchi M, Mennju T, Nakayama E, Kobayashi M, Kikuchi R, Kitamura J, Imamura N, Huang CL, Date H
  • Journal Title: Lung Cancer Volume: 76 Pages: 431-438
• [Journal Article] Clinicopathological characteristics of surgically resected pulmonary pleomorphic carcinoma (2012)
  • Author(s): Chen F, Sonobe M, Sato T, Sakai H, Huang CL, Bando T, Date H
  • Journal Title: Eur J Cardiothorac Surg Volume: 41 Pages: 1037-1042
• [Journal Article] Expression of IGF1R is associated with tumor differentiation and survival in patients with lung adenocarcinoma (2012)
  • Author(s): Kikuchi R, Sonobe M, Kobayashi M, Ishikawa M, Kitamura J, Nakayama E, Menju T, Miyahara R, Huang CL, Date H
  • Journal Title: Ann Surg Oncol Volume: 3 Pages: 412-420
• [Journal Article] Short-term outcome in living donors forlung transplantation : the role of preoperative computer tomographic evaluations of fissures and vascular anatomy (2012)
  • Author(s): Chen F, Fujinaga T, Shoji T, Kubo T, Sonobe M, Sato M, Aoyama A, Sato T, Sakai H, Bando T, Date H
  • Journal Title: Transpl Int Volume: 25 Pages: 732-738
• [Journal Article] Outcomes and pulmonary function in living lobar lung transplant donors (2012)
  • Author(s): Chen F, Fujinaga T, Shoji T, Sonobe M, Sato T, Sakai H, Bando T, Date H
  • Journal Title: Transpl Int Volume: 25 Pages: 153-157
• [Journal Article] Intratumoral Wnt2B expression affects tumor proliferation and survival in malignant pleural mesothelioma patients. (2012)
  • Author(s): Kobayashi M, Date H, et al.
  • Journal Title: Experimental and Therapeutic Medicine Volume: 3 Pages: 952-958
  • Peer Reviewed
• [Journal Article] Expression of IGF1R is associated with tumor differentiation and survival in patients with lung adenocarcinoma. (2012)
  • Author(s): Kikuchi R, Date H, et al.
  • Journal Title: Annals of Surgical Oncology Volume: 3 Pages: 412-420
  • Peer Reviewed
• [Journal Article] Clinical significance of BRAF gene mutations in patients with non-small cell lung cancer (2011)
  • Author(s): Kobayashi M, Sonobe M, Takahashi T, Yoshizawa A, Ishikawa M, Kikuchi R, Okubo K, Huang CL, Date H
  • Journal Title: Anticancer Res Volume: 31 Pages: 4619-4623
• [Journal Article] Impact of KRAS and EGFR gene mutations on recurrence and survival in patients with surgically resected lung adenocarcinomas (2011)
  • Author(s): Sonobe M, Date H, et al.
  • Journal Title: Annals of Surgical Oncology Volume: - Issue: S3 Pages: 347-354
  • DOI: 10.1245/s10434-011-1799-8
  • Peer Reviewed
• [Journal Article] Expression of IGF1R is associated with tumor proliferation and survival in patients with lung adenocarcinoma (2011)
  • Author(s): Kikuchi R, Date H, et al.
  • Journal Title: Annals of Surgical Oncology Volume: - Issue: S3 Pages: 412-420
  • DOI: 10.1245/s10434-011-1878-x
  • Peer Reviewed
• [Journal Article] Clinical significance of BRAF gene mutations in patients with non-small cell lung cancer (2011)
  • Author(s): Kobayashi M, Date H, et al.
  • Journal Title: Anticancer Research Volume: 31 Pages: 4619-4623
  • Peer Reviewed
• [Presentation] Ad-shWnt2B 胸腔内投与モデルに対するIVIS を用いた治療評価 (2013)
  • Author(s): 小林正嗣、黄 政龍、菊地柳太郎、今村直人、志熊 啓、曽和輝正、園部 誠、伊達洋至
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-04
• [Presentation] Snail expression is associated with epithelial to mesenchymal transition and a poor prognosis in malignant pleural mesotheliomas (2012)
  • Author(s): Masashi K, Huang CL, Sonobe M, Kikuchi R, Ishikawa M, Imamura N, Kitamura J, Iwakiri S, Itoi K, Yasumizu R, Date H
  • Organizer: AACR 103rd Annual Meeting
  • Place of Presentation: Chicago, U.S.A.
  • Year and Date: 2012-04-04
• [Presentation] FGFR2 gene amplification and overexpression frequently occur in squamous cell carcinomas of the lung (2012)
  • Author(s): Kikuchi R, Date H, et al.
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Chicago, U.S.A.
• [Presentation] 非小細胞肺癌におけるWnt familyの腫瘍内発現の臨床的検討 (2011)
  • Author(s): 黄 政龍、中島成泰、横見瀬裕保、小林正嗣、菊地柳太郎、石川将史、今村直人、園部 誠、伊達洋至
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-04
• [Presentation] 肺癌における腫瘍内Wnt 発現とWnt 抑制遺伝子治療 (2011)
  • Author(s): 黄 政龍、劉 大革、中島成泰、横見瀬裕保、小林正嗣、菊地柳太郎、石川将史、堀内真理佳、園部 誠、伊達洋至
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] TS 抑制shRNA 発現アデノウィルスベクターの抗腫瘍効果の検討 (2011)
  • Author(s): 黄 政龍、劉 大革、横見瀬裕保、伊達洋至、和田洋巳
  • Organizer: 第28回日本呼吸器外科学会総会
  • Place of Presentation: 大分
  • Year and Date: 2011-05-13
• [Presentation] 悪性胸膜中皮腫においてWnt2B は腫瘍増殖に影響する (2011)
  • Author(s): 小林正嗣、黄 政龍、喜多村次郎、菊地柳太郎、石川将史、毛受暁史、園部 誠、宮原 亮、伊達洋至
  • Organizer: 第28回日本呼吸器外科学会総会
  • Place of Presentation: 大分
  • Year and Date: 2011-05-13
• [Presentation] 非小細胞肺癌におけるFGFR2 発現の検討 (2011)
  • Author(s): 菊地柳太郎、喜多村次郎、石川将史、小林正嗣、中山 英、毛受暁史、園部 誠、宮原 亮、黄 政龍、伊達洋至
  • Organizer: 第28回日本呼吸器外科学会総会
  • Place of Presentation: 大分
  • Year and Date: 2011-05-13
• [Presentation] Overexpression of FGFR2 gene is associated with advanced stage squamous cell carcinoma of the lung (2011)
  • Author(s): Kikuchi R, Huang CL, Miyahara R, Sonobe M, Menju T, Kobayashi M, Ishikawa M, Kitamura J, Date H
  • Organizer: AACR 102nd Annual Meeting
  • Place of Presentation: Orlang, U.S.A.
  • Year and Date: 2011-04-02
• [Presentation] The intratumoral Wnt2B expression affects tumor progression in malignant pleural mesotheliomas (2011)
  • Author(s): Kobayashi M, Huang CL, Miayahara R, Sonobe M, Menju T, Kikuchi R, Ishikawa M, Kitamura J, Itoi K, Date H
  • Organizer: AACR 102nd Annual Meeting
  • Place of Presentation: Orlang, U.S.A.
  • Year and Date: 2011-04-02
• [Remarks]
  • URL: http://www.thoracic-kyoto-u.gr.jp/